EVIDENCE FOR A ROLE OF FREE-RADICALS BY SYNTHESIZED SCAVENGER, 2-OCTADECYLASCORBIC ACID, IN CERULEIN-INDUCED MOUSE ACUTE-PANCREATITIS

To define the role of free radicals and of lipid peroxide involvement during the progress of cerulein-induced acute pancreatitis in mice, we evaluated the effect of a novel free radical scavenger, 2-octadecylascorbic acid (CV-3611), on pancreatic edema formation, and the levels of serum enzymes (amylase, lipase) and of lipid peroxide in pancreatic tissue. Mice were divided into three groups: control group, intraperitoneal injection of saline only; pancreatitis group, cerulein 50-mu-g/kg injected intraperitoneally six times at 1-hr intervals; treatment group, CV-3611 10 mg/kg subcutaneously just after intraperitoneal cerulein injection. After the cerulein injection, the degree of pancreatic edema formation, serum amylase and lipase levels, and the amount of lipid peroxide in pancreatic tissue increased significantly during the observation period of 12 hr. Treatment with CV-3611 resulted in significant reduction in pancreatic edema formation at 3.5 hr (P < 0.05) and 9 hr (P < 0.05), serum amylase and lipase levels at 3.5 hr (P < 0.05) and 12 hr (P < 0.05), and lipid peroxide levels at 3.5 hr (P < 0.05), 6 hr (P < 0.05) and 12 hr (P < 0.05). These results indicate that a novel free radical scavenger, CV-3611, has a strong therapeutic effect during the development of acute pancreatitis and suggest that oxygen-derived free radicals play an important role in the pathogenesis of acute pancreatitis.